Urinary Bisphenol A Research Articles

From Oxidative Stress to Male Infertility: Review of the Associations of Endocrine-Disrupting Chemicals (Bisphenols, Phthalates, and Parabens) with Human Semen Quality.

Exposure to endocrine-disrupting chemicals (EDCs) may result in oxidative stress and endocrine system disturbance, which can have an impact on human reproduction and development. In male reproductive health, EDCs have been related to impaired reproductive function and male infertility, altered fetal development, and testicular germ-cell, prostate, and breast cancers. We conducted an electronic search using PubMed on endocrine disruptors related to oxidative stress and male infertility, and evaluated their association with endocrine-disrupting chemicals (bisphenols, phthalates, and parabens) in 25 articles. Higher levels of urinary bisphenols showed correlation with impaired semen quality and increased DNA damage. Considering phthalates and their metabolites, all studies found a positive association between urinary levels of phthalates and at least one semen parameter indicative of low semen quality; some studies also revealed sperm DNA damage. The studies on parabens less often revealed correlation of urinary parabens concentrations with a decrease in sperm count, as well as motility and DNA damage. Moreover, EDCs can elevate ROS production and lipid peroxidation, increase apoptosis, induce epigenetic modifications, and change the Y:X sperm chromosome ratio and sperm protein composition. Our review revealed detrimental effects of EDCs on semen quality and sperm DNA integrity—especially in BPA and phthalates, but also in parabens.

Phthalate and bisphenol a exposures during pregnancy: Findings from the National Children's Study

Maternal exposure to phthalates and bisphenol A (BPA) during pregnancy can result in many adverse offspring health outcomes. Exposure to phthalates and BPA can vary depending on consumption of certain foods, some of which may vary by race/ethnicity. This study relates urine phthalate and BPA concentrations to sociodemographic and diet data. Concentrations of bisphenol A (BPA) and 11 phthalate metabolites were measured from spot urine at the third trimester visit of a sample of 485 pregnant women from the National Children's Study Vanguard Study Pilot data from seven U.S. cities. At the same time, food frequency questionnaires (FFQ) using the Diet*Calc software were obtained from 313 (65%) participants to assess dietary behavior. Overall, phthalate metabolites were highest among Hispanic women, particularly mBP, miBP, and mECPP, and these disparities were not explained by diet. Participants who did not attend college had higher concentrations of mBP, mBzP, mEP, and miBP, and lower mCOP. These disparities were also not explained by diet. The causes for these disparities should be further studied to reduce potential negative health outcomes associated with phthalate exposure for children of Hispanic or non-college educated women.

Associations of maternal urinary bisphenol and phthalate concentrations with offspring reproductive development

Fetal exposure to bisphenols and phthalates may influence development of the reproductive system. In a population-based, prospective cohort study of 1059 mother-child pairs, we examined the associations of maternal gestational urinary bisphenols and phthalates concentrations with offspring reproductive development from infancy until 13 years. We measured urinary bisphenol and phthalate concentrations in each trimester. We obtained information on cryptorchidism or hypospadias after birth from medical records. At 9.7 years, we measured testicular and ovarian volume by MRI. At 13.5 years, we measured child Tanner stages and menstruation through questionnaire. We performed linear or logistic regression models for boys and girls to assess the associations of maternal urinary average and trimester-specific bisphenols and phthalates with child reproductive outcomes. Next, to further explore potential synergistic or additive effects of exposures together, we performed mixed exposure models using a quantile g computation approach. Models were adjusted for maternal age, ethnicity, body-mass index, education, parity, energy intake, smoking and alcohol use, and child's gestational age at birth, birthweight and body-mass index. In boys, no associations of maternal gestational phthalate or bisphenol with offspring cryptorchidism and hypospadias were found. Higher maternal high-molecular-weight phthalate and total bisphenol, but not phthalic acid or low-molecular-weight phthalate, were associated with larger child testicular volume at 10 years. Higher maternal phthalic acid and total bisphenol were associated with earlier genital and pubic hair development at 13 years, respectively (p-values<0.05). In girls, we found no associations of maternal urinary bisphenol and phthalate with ovarian volume or menstrual age. Only higher maternal urinary high-molecular-weight phthalate was associated with earlier pubic hair development at 13 years (p-values <0.05). Higher mixture exposure was associated with earlier pubic hair development in both sexes. In conclusion, higher maternal gestational urinary bisphenol and phthalate concentrations were associated with alterations in offspring reproductive development, mainly in boys.

Does Older Age Modify Associations between Endocrine Disrupting Chemicals and Fecundability?

Urinary concentrations of several endocrine disrupting chemicals, including phthalate metabolites, bisphenol A (BPA), and benzophenone (BP)-type ultraviolet (UV) filters, have been associated with a longer time-to-pregnancy (TTP). Potential modification of these associations by couple’s age has not been studied. TTP was defined as the number of prospectively observed menstrual cycles a couple attempted pregnancy until the occurrence of a human chorionic gonadotropic-detected pregnancy. Urinary concentrations of two BP-type UV filters and three phthalate metabolites were measured at baseline. Fecundability odds ratios (FORs) and 95% confidence intervals (CIs) were estimated for each chemical adjusting for age, body mass index, serum cotinine, creatinine, and accounting for right censoring and left truncation. Models evaluated effect modification between EDC concentrations and TTP by partner’s age, dichotomized at 35 years. Separate models were run for male and female partners. No significant effect modification was observed for any EDC for either partner, but data were suggestive of a longer TTP among females aged ≥35 years, particularly for BP-2 (FOR = 0.61, 95% CI 0.36, 1.05) and 4-hydroxybenzophenone (FOR = 0.71, 95% CI: 0.46, 1.09) reflecting 39% and 29% reductions in fecundability, respectively. We saw no evidence of effect modification by couples’ age on associations between TTP and urinary phthalate or BPA metabolite concentrations. Across the EDCs we examined, we found little evidence that age modifies TTP-exposure associations.

Maternal urinary concentrations of bisphenol A during pregnancy are associated with global DNA methylation in cord blood of newborns in the “NELA” birth cohort

Endocrine disrupting chemicals (EDCs) set a public health risk through disruption of normal physiological processes. The toxicoepigenetic mechanisms of developmental exposure to common EDCs, such as bisphenol A (BPA), are poorly known. The present study aimed to evaluate associations between perinatal maternal urinary concentrations of BPA, bisphenol S (BPS) and bisphenol F (BPF) and LINE-1 (long interspersed nuclear elements) and Alu (short interspersed nuclear elements, SINEs) DNA methylation levels in newborns, as surrogate markers of global DNA methylation. Data come from 318 mother-child pairs of the `Nutrition in Early Life and Asthma´ (NELA) birth cohort. Urinary bisphenol concentration was measured by dispersive liquid–liquid microextraction and ultrahigh performance liquid chromatography with tandem mass spectrometry detection. DNA methylation was quantitatively assessed by bisulphite pyrosequencing on 3 LINEs and 5 SINEs. Unadjusted linear regression analyses showed that higher concentration of maternal urinary BPA in 24th week's pregnancy was associated with an increase in LINE-1 methylation in all newborns (p = 0.01) and, particularly, in male newborns (p = 0.03). These associations remained in full adjusted models [beta = 0.09 (95 % CI = 0.03; 0.14) for all newborns; and beta = 0.10 (95 % CI = 0.03; 0.17) for males], including a non-linear association for female newborns as well (p-trend = 0.003). No associations were found between maternal concentrations of bisphenol and Alu sequences. Our results suggest that exposure to environmental levels of BPA may be associated with a modest increase in LINE-1 methylation -as a relevant marker of epigenomic stability- during human fetal development. However, any effects on global DNA methylation are likely to be small, and of uncertain biological significance.

Prenatal bisphenol A exposure in relation to behavioral outcomes in girls aged 4–5 and modification by socio-demographic factors in The Infant Development and Environment Study (TIDES)

Bisphenol A (BPA) is a polymer used in the production of polycarbonate plastics and epoxy resins. An estrogen mimic, prenatal BPA exposure has been associated with several behavioral outcomes in children; however, the impact of maternal demographic and economic factors on associations between BPA and child behavioral outcomes have not been examined. The objective of this study was to examine associations between prenatal maternal urinary BPA and behavior in 4–5 year old girls, and to assess whether socio-demographic factors modify this relationship. Mothers enrolled in The Infant Development and Environment Study (TIDES) provided a single spot urine at enrollment (median gestational age 11 weeks) and completed the Behavior Assessment System for Children-2 (BASC-2) and Social Responsiveness Scale-2 (SRS-2) when their daughters were 4–5 years of age. Mother-daughter pairs with complete phthalate, BASC-2, SRS-2, and covariate data were included in this analysis (N = 244). BPA was detectable in 93 % of urine samples. We used multivariable linear regression analyses to estimate associations between maternal urinary log10-transformed BPA concentration and BASC-2 subscale and composite scores and SRS-2 Total Score. To examine the role of socioeconomic and demographic factors associated with study site, we stratified by TIDES center, comparing those enrolled at University of Rochester Medical Center (URMC), a predominately lower socioeconomic population, and those enrolled elsewhere: University of Washington, University of Minnesota, and University of California San Francisco, whose populations share similar higher socioeconomic demographic characteristics. Across all centers, no associations were seen between BPA and BASC-2 or SRS-2 scores. When stratifying by center, BPA was significantly associated with greater social impairment as measured by the SRS-2 Total Score (β-coefficient [95 % confidence intervals]: 5.1 [1.0, 9.2]) in URMC participants (N = 61). In non-URMC participants (N = 183), BPA was significantly associated with lower BASC-2 Internalizing composite (−3.3 [−6.7, 0.0]) and Depression subscale scores (−3.4 [−6.7, 0.0]) while no associations were seen between BPA and SRS-2 scores. Our findings suggest that sociodemographic factors may modify the impacts of maternal prenatal BPA on developmental endpoints.

Bisphenol A exposures and hormone concentrations in a cohort of women receiving aromatase inhibitor therapy for breast cancer.

e12535 Background: Bisphenol A (BPA), a widely used chemical in plastics production, has been shown to have estrogenic activity, although it is unclear whether BPA exposure alters effectiveness of aromatase inhibitor (AI) treatment among women with breast cancer. In vitro studies have indicated that at higher concentrations (≥10-4 μM), BPA inhibits aromatase expression and activity, whereas at environmentally relevant concentrations (≤10-8 μM), BPA increases aromatase expression and activity. Few in vivo studies have investigated the association between BPA exposure and estrogen concentrations among non-pregnant women. This pilot study among post-menopausal women receiving AI therapy evaluated whether BPA is detectable in participants’ urine, and the association between BPA and hormone concentrations. Methods: This study was ancillary to a larger intervention study (ClinicalTrials.gov NCT01509079), and participants provided informed consent for this ancillary study under a protocol approved by the institutional review boards of Park Nicollet Institute/HealthPartners and the University of Minnesota. AI adherence during the 4 weeks prior to the baseline visit was monitored through weekly diaries. Participants were instructed to collect spot urine collections in sterile, BPA-free polypropylene containers in the 24 hours prior to the baseline study visit. Serum hormone concentrations were measured using serum collected at the baseline study visit. The Breast Cancer Prevention Trial - Musculoskeletal Symptom (BCPT-MS) scale was used to assess AI-associated musculoskeletal syndrome symptoms at the baseline study visit. Results: Fourteen women agreed to participate in the pilot study, however one participant’s data was excluded due to substances interfering with BPA measurement. BPA was detected in urine from all 13 remaining participants. Geometric mean urinary BPA concentration (1.55 mcg/g creatinine, 95% confidence interval (CI): 0.98-2.45) was higher than concentrations reported for females (1.36 mcg/g creatinine, 95% CI: 1.23-1.51) in the 2013-14 National Health and Nutrition Examination Survey biomonitoring data. Age, body mass index, and percent body fat did not differ between women above or below the study median urinary BPA concentrations (1.49 ng/mL). Women with BPA concentrations &gt;1.49 ng/mL had consistently lower serum estrone (5.0 vs. 7.0 pg/mL, p=0.15), estradiol (2.8 vs. 3.6 pg/mL, p=0.04), and testosterone (21.5 vs 23.8 ng/dL, p=0.28) concentrations compared to women with lower BPA concentrations. No statistically significant differences in BCPT-MS scores were observed between women with higher vs. lower urinary BPA concentrations. Conclusions: These preliminary findings suggest that BPA exposures may work in concert with AIs to lower serum estrogen levels. However, further research is needed to confirm these findings.

Bisphenol A correlates with fewer retrieved oocytes in women with tubal factor infertility

Serum and urinary bisphenol A (BPA) concentrations have been associated negatively with the number of retrieved oocytes after in vitro fertilization (IVF). The impact of BPA upon women with polycystic ovary syndrome (PCOS) and women with tubal factor infertility (TFI), following IVF, was investigated. To this purpose, associations among serum and urinary and follicular fluid (FF) BPA concentrations and the number of retrieved and fertilized oocytes and comparisons between pregnancy rates were evaluated. This was a cross-sectional study conducted at a university-affiliated assisted conception unit between January and November 2019, including 93 women of reproductive age (PCOS: 45; TFI: 48) following IVF. Unconjugated FF and serum BPA concentrations and total urinary BPA concentration were measured using a novel gas chromatography-mass spectrometry method. The number of retrieved and fertilized oocytes and pregnancy rate were documented and evaluated. The number of oocytes retrieved from PCOS women was greater than that of 21 TFI women, independently of BMI. Lower FF BPA concentrations were found in all PCOS women and in overweight/obese PCOS compared to TFI women (0.50, 0.38, and 1.13ng/mL, respectively). In TFI women, FF BPA concentrations correlated negatively with the number of retrieved oocytes. Serum and FF and urinary BPA concentrations did not significantly affect the number of fertilized oocytes and pregnancy rate in both groups. FF BPA concentrations were lower in all PCOS women and in overweight/obese PCOS than in TFI women. In TFI women, FF BPA concentrations correlated negatively with retrieved oocytes. Confirmation of these findings might lead to moderation of use of BPA-containing products by women undergoing IVF.

Pregnancy urinary concentrations of bisphenol A, parabens and other phenols in relation to serum levels of lipid biomarkers: Results from the EARTH study

The epidemiologic literature on associations between urinary phenol concentrations and lipid profiles during pregnancy is limited. We examined whether urinary concentrations of phenol and phenol replacement biomarkers were associated with serum lipid levels among pregnant women. This cross-sectional study included 175 women attending the Massachusetts General Hospital Fertility Center who enrolled in the Environment and Reproductive Health (EARTH) Study between 2005 and 2017 and had data available on urinary phenol biomarkers and serum lipids during pregnancy. We used linear regression models to assess the relationship between groups of urinary phenol and phenol replacement biomarkers and serum lipid levels [total cholesterol, high density lipoprotein (HDL), non-HDL, low-density lipoprotein (LDL) cholesterol, and triglycerides], while adjusting for age at sample collection, pre-pregnancy BMI, education, race, infertility diagnosis, cycle type, number of fetuses, trimester and specific gravity. In adjusted models, pregnant women with urinary propylparaben concentrations in the highest tertile had 10% [22 (95% CI = 5, 40) mg/dL], 12% [19 (95% CI = 2, 36) mg/dL] and 16% [19 (95% CI = 3, 35) mg/dL] higher mean total, non-HDL and LDL cholesterol, respectively, compared to women with concentrations in the lowest tertile. Similar elevations were observed for urinary bisphenol A concentrations. Urinary bisphenol S, benzophenone-3, triclosan, methylparaben, ethylparaben, and butylparaben were unrelated to serum lipids. Among pregnant women, urinary concentrations of bisphenol A and propylparaben were associated with higher serum levels of total, non-HDL and LDL cholesterol.

Associations of Phthalate Metabolites and Bisphenol A Levels with Obesity in Children: The Korean National Environmental Health Survey (KoNEHS) 2015 to 2017.

BackgroundPhthalates and bisphenol A (BPA) are synthetic chemicals widely used in daily life. This study investigated urinary phthalate and BPA levels in Korean children and their associations with obesity. MethodsA total of 2,351 children aged 3 to 17 years who participated in the Korean National Environmental Health Survey 2015 to 2017 were included. Urinary dilution was corrected using covariate-adjusted standardization (CAS). We examined the geometric mean (GM) concentrations of urinary phthalate metabolites, including di (2-ethylhexyl) phthalate (DEHP) metabolites (mono [2-ethyl-5-hydroxyhexyl] phthalate, mono [2-ethyl-5-oxohexyl] phthalate, and mono [2-ethyl-5-carboxypentyl] phthalate [MECPP]), mono-benzyl-phthalate (MBzP), mono (carboxyoctyl) phthalate (MCOP), mono (carboxy-isononyl) phthalate (MCNP), mono (3-carboxypropyl) phthalate, and mono-n-butyl-phthalate (MnBP), and BPA. We also analyzed the odds ratio (OR) for obesity according to the quartiles of each analyte. ResultsThe urinary GM levels of DEHP metabolites and MnBP were notably higher among Korean children than among American, Canadian, and German children. The CAS-applied GM concentrations of most analytes, except for MBzP, MCOP, and MCNP, were higher in children aged 3 to 5 years than in those aged 6 to 17 years. The OR for obesity in the highest quartile of MECPP was significantly higher than in the lowest quartile after adjusting for covariates. However, the other phthalate metabolites and BPA were not significantly associated with obesity. ConclusionThe concentrations of urinary DEHP metabolites and MnBP were higher in Korean children than in children in Western countries. Urinary MECPP exposure, but not other phthalates or BPA, showed a positive association with obesity in Korean children. Further studies are required to elucidate the causal relationships.

Maternal Phthalate and Bisphenol Urine Concentrations during Pregnancy and Early Markers of Arterial Health in Children.

Background:Fetal exposure to endocrine-disrupting chemicals such as phthalates and bisphenols might lead to fetal cardiovascular developmental adaptations and predispose individuals to cardiovascular disease in later life.Objectives:We examined the associations of maternal urinary bisphenol and phthalate concentrations in pregnancy with offspring carotid intima-media thickness and distensibility at the age of 10 y.Methods:In a population-based, prospective cohort study of 935 mother–child pairs, we measured maternal urinary phthalate and bisphenol concentrations at each trimester. Later, we measured child carotid intima-media thickness and distensibility in the children at age 10 y using ultrasound.Results:Maternal urinary average or trimester-specific phthalate concentrations were not associated with child carotid intima-media thickness at age 10 y. Higher maternal average concentrations of total bisphenol, especially bisphenol A, were associated with a lower carotid intima-media thickness [differences standard deviation score and 95% confidence interval (CI): , and (95% CI: , ) per interquartile range (IQR) increase in maternal urinary total bisphenol and bisphenol A concentration]. Trimester-specific analysis showed that higher maternal third-trimester total bisphenol and bisphenol A concentrations were associated with lower child carotid intima-media thickness [differences (95% CI: , ) and (95% CI: , ) per IQR increase in maternal urinary bisphenol concentration]. Maternal urinary bisphenol or phthalate concentrations were not associated with child carotid distensibility.DISCUSSION:In this large prospective cohort, higher maternal urinary bisphenols concentrations were associated with smaller childhood carotid intima-media thickness. Further studies are needed to replicate this association and to identify potential underlying mechanisms. https://doi.org/10.1289/EHP10293

Serum vitamin D level mitigates fractional exhaled nitric oxide linked to bisphenol-A in school-aged children.

Previous studies on the relationship of bisphenol-A (BPA) with fractional exhaled nitric oxide (FeNO) had conflicting results, suggesting that other factors may modulate this relationship. Thus, we investigated the modulating effect of vitamin D on the relationship of BPA with FeNO in children. This study recruited 432 children (10 to 12 years old) from the general pediatric population of Korea between June and July 2017. We conducted measurements of urinary BPA, serum vitamin D, specific serum IgE, FeNO, and data from impulse oscillometry (reactance area [AX], airway resistance at 5 Hz [Rrs5] and 20 Hz [Rrs10], and the difference of Rrs5 and Rrs20 [Rrs5-20]). Serum vitamin D (adjusted β =- 0.014, p=0.002) and urinary BPA (β = 0.006, p<0.001) level was significantly associated with FeNO. Urinary BPA level was significantly associated with FeNO in children with low vitamin D levels (≤23 ng/mL; αβ = 0.006, p < 0.001), but not in children with high vitamin D levels (>23 ng/mL). The interaction of vitamin D and BPA had a significant effect on FeNO (pint = 0.005). There was no relationship with the airway lung function (Rrs5, AX, and Rrs5-20) to serum vitamin D and urinary BPA level. Vitamin D ameliorated the BPA-mediated increase of FeNO in children. These results suggest that children with low vitamin D levels may be more susceptible to airway inflammation due to BPA.

Associations between urinary bisphenol A and its analogues and semen quality: A cross-sectional study among Chinese men from an infertility clinic.

Human studies on association between bisphenol A (BPA) exposure and semen quality, mostly based on single urinary measurement, are inconsistent. There is limited human evidence on BPA analogues such as bisphenol F (BPF) and bisphenol S (BPS), and little is known on potential effects of bisphenol mixtures. We aimed to explore whether individual or mixtures of BPA, BPS and BPF assessed in repeated urinary measurements were associated with semen quality among 984 Chinese men from an infertility clinic. We found that higher BPA exposure was associated with increased odds ratios (ORs) of having below-reference sperm concentration, total sperm count, progressive motility and total motility (all P for trends<0.05). Higher BPS exposure was associated with increased ORs of having below-reference progressive motility and total motility (both P for trends=0.02); the ORs comparing extreme quartiles were 1.62 (95% CI: 1.07, 2.43) and 1.57 (95% CI: 1.06, 2.33), respectively. Elevated risks for each outcome were also observed when bisphenol mixtures were at≥55th percentiles. For semen quality parameters modeled as continuous outcomes, inverse associations with individual BPA and BPS and bisphenol mixtures were still estimated. Our results suggested that higher exposure to individual BPA and BPS and bisphenol mixtures were associated with impaired semen quality.

Levels of parabens and bisphenols in personal care products and urinary concentrations in Indian young adult women: Implications for human exposure and health risk assessment

Limited information is available about the levels of exposure of paraben and bisphenols emerging from personal care products (PCPs) use in Indian women and the risk associated with it. In this study, liquid chromatography-tandem mass spectrometry (LC-MS/MS) was used to determine the concentrations of six parabens (methyl-, ethyl-, propyl-, butyl, benzyl-, and heptyl-parabens) and 8 bisphenols (Bisphenol A, B, F, P, S, Z, AP, and AF) in PCPs samples (n = 114) obtained from Indian market and in the urine samples of young adult females (n = 52). The concentrations measured in PCPs and urine samples were used to determine the estimated daily intake. The mean concentrations of 6 parabens and 8 bisphenols in PCPs ranged from 38.3 to 2.38 × 105 ng/g and 2.71–148 ng/g, respectively. In urine samples analysed, the mean concentrations of 6 parabens and 8 bisphenols ranged from 0.007 to 293 ng/mL and 0.10–10.8 ng/mL, respectively. There was no significant correlation of EDCs with age, BMI and waist-to-hip ratio (WHR), but significant correlations (p < 0.05) were observed between urinary paraben and bisphenol concentrations. A statistically significant difference (p < 0.05) exists between the BMI and WHR groups by bisphenol concentrations. Estimated daily intake and exposure risks for parabens and bisphenols revealed no possible concerns for Indian young adult females. Hitherto, this is the first study to show that Indian young adult females were exposed to parabens and bisphenols. This study provides evidence on PCPs usage contribute to the urinary concentrations of EDCs.

Triglyceride profiles are associated with subacute exposure to bisphenol A in healthy young adults

Conflicted results from previous epidemiological studies call for mechanistic evidence to associate exposure to bisphenol A (BPA) with cardiometabolic diseases. In this natural experiment among healthy travelers from Los Angeles (LA) to Beijing, we collected paired urine and blood samples before their departure, 6–8 weeks after their arrival to Beijing, and 4–7 weeks after their return to LA for the assessment of urinary BPA and lipidome in the serum fraction of blood, to study the effects of drastically changed BPA exposure on the lipid metabolism in relation to the development of cardiometabolic disorders. We used linear mixed-effects models with random intercepts for participant and phase to examine the associations between urinary BPA and serum lipidome. Among 744 lipid species from seven classes, triglyceride (TGs) species showed the strongest associations with BPA exposure. The elevation in BPA exposure was associated with increases in TGs with short carbon chains or few double bonds, and decreases in TGs with long carbon chains or many double bonds. A significant linear relationship was observed between BPA-associated TG changes and the number of carbons and double-bonds in the acyl chain. No modification effects of gender but of body mass index (BMI) were observed on the associations between BPA exposure and TGs. This interdisciplinary environmental research substantiated the cardiometabolic effects of BPA according to the perturbations of TG profiling.

Assessment of Exposure to Di-(2-ethylhexyl) Phthalate (DEHP) Metabolites and Bisphenol A (BPA) and Its Importance for the Prevention of Cardiometabolic Diseases.

Exposomics analyses have highlighted the importance of biomonitoring of human exposure to pollutants, even non-persistent, for the prevention of non-communicable diseases such as obesity, diabetes, non-alcoholic fatty liver disease, atherosclerosis, and cardiovascular diseases. Phthalates and bisphenol A (BPA) are endocrine disrupting chemicals (EDCs) widely used in industry and in a large range of daily life products that increase the risk of endocrine and cardiometabolic diseases especially if the exposure starts during childhood. Thus, biomonitoring of exposure to these compounds is important not only in adulthood but also in childhood. This was the goal of the LIFE-PERSUADED project that measured the exposure to phthalates (DEHP metabolites, MEHP, MEHHP, MEOHP) and BPA in Italian mother–children couples of different ages. In this paper we describe the method that was set up for the LIFE PERSUADED project and validated during the proficiency test (ICI/EQUAS) showing that accurate determination of urinary phthalates and BPA can be achieved starting from small sample size (0.5 mL) using two MS techniques applied in cascade on the same deconjugated matrix.

Within- and between-person variability of urinary phthalate metabolites and bisphenol analogues over seven days: Considerations of biomonitoring study design

Urine was used as a part of a human biomonitoring study based on the excretion kinetics of less-persistent contaminants, such as phthalates and bisphenol A (BPA). Despite the advantages of being non-invasive and easy to collect, urine can show a large variability of concentrations of phthalate metabolites and BPA within a person depending on sampling time. Therefore, it is essential to assess the variability of urinary concentrations for comprehensive sampling design in the context of exposure and risk assessments. In this study, 18 phthalate metabolites and eight BPs were measured in all spot urine (n = 401) collected from 12 participants for seven consecutive days to evaluate within- and between-person variabilities. The intraclass correlation coefficients (ICCs) for all spot urines were poor for monomethyl phthalate (ICC: 0.002) and BPA (0.121) but were moderate for monoethyl phthalate (0.514) and monobenzyl phthalate (0.462). Based on the results of di (2-ethylhexyl) phthalate (DEHP) metabolites, the half-life and differences in metabolic capability seem to affect the ICCs. Urinary mono (2-ethylhexyl) phthalate (MEHP), a primary metabolite of DEHP, was suggested as a short-term exposure marker of DEHP in our study. Creatinine- and specific gravity-adjusted concentrations of phthalate metabolites and BPs resulted in increased ICCs, implying requirements for randomly collected spot urine. Most analytes in the first morning voids (FMVs) were correlated significantly with those in the daily composites, suggesting the feasibility of FMVs to estimate the daily exposure dose. This study facilitates a more comprehensive sampling design and data interpretation strategy for human biomonitoring studies.

Associations of mid-childhood bisphenol A and bisphenol S exposure with mid-childhood and adolescent obesity.

Background:Bisphenol A (BPA) is a suspected obesogen that has been associated with adiposity in children. Bisphenol S (BPS), a structural analog of BPA, is used as a BPA substitute and may have similar health effects as BPA. However, few studies have examined whether BPS is associated with childhood adiposity.Methods:We quantified urinary BPA and BPS concentrations in 212 children age 8 years from the HOME Study, a prospective pregnancy and birth cohort study that enrolled pregnant women in Cincinnati, Ohio (2003–2006). We assessed children’s adiposity by bioelectric impedance at age 8 years (n = 212), and by anthropometry and dual-energy X-ray absorptiometry at age 12 years (n = 181). We measured serum adipocytokine concentrations at age 12 years (n = 155). Using multivariable linear regression, we estimated covariate-adjusted associations of BPA and BPS with adiposity measures at ages 8 and 12 years and adipocytokine concentrations at age 12 years.Results:Each 10-fold increase in urinary BPA concentrations were inversely associated with percent body fat at age 8 years [β = −1.2, 95% confidence interval (CI) = −3.4, 1.0] and 12 years (β = −1.6, 95% CI = −4.0, 0.9). In contrast, urinary BPS concentrations were positively associated with percent body fat at age 8 years (β = 1.1, 95% CI = −0.6, 2.7), but not at 12 years (β = 0.1, 95% CI = −1.7, 1.8). Urinary BPA and BPS concentrations were not associated with serum adiponectin or leptin concentrations.Conclusions:We did not observe evidence that urinary BPA or BPS concentrations during childhood were associated with greater child adiposity at ages 8 and 12 years in this cohort.

Cross-Sectional Association of Urinary Bisphenol A and Vaccine-Induced Immunity against Hepatitis B Virus: Data from the 2003-2014 National Health and Nutrition Examination Survey.

Hepatitis B virus (HBV) infection poses a serious health burden; bisphenol A (BPA), a commonly used plasticizer for consumer products, is a potential immune disruptor. However, epidemiologic studies revealing the association between BPA exposure and immunity are limited. This study investigates the association between environmental BPA exposure and immune response following HBV vaccination in a nationally representative sample population. Using National Health and Nutrition Examination Survey data from six cycles, we analyzed the data of 6134 participants, classified as susceptible to HBV infection (n = 3086) or as having vaccine-induced immunity (n = 3048). Associations between BPA level and HBV susceptibility were assessed using multivariable logistic regression and expressed as odds ratios (ORs) of the pooled data and data for each cycle. There was a significant association in the pooled data after adjusting for potential confounders (adjusted OR (aOR): 1.14, 95% confidence interval (CI): 1.05–1.23). However, the associations between BPA concentration and HBV susceptibility were inconsistent across the survey cycles and tended to decrease in more recent cycles. Although this study preliminarily suggests that BPA attenuates the immune response to hepatitis B vaccination, further prospective studies are warranted to elucidate the discrepancies observed.

Urinary concentrations of phenols, oxidative stress biomarkers and thyroid cancer: Exploring associations and mediation effects

Phenols have been shown to influence the cellular proliferation and function of thyroid in experimental models. However, few human studies have investigated the association between phenol exposure and thyroid cancer, and the underlying mechanisms are also poorly understood. We conducted a case-control study by age- and sex-matching 143 thyroid cancer and 224 controls to investigate the associations between phenol exposures and the risk of thyroid cancer, and further to explore the mediating role of oxidative stress. We found that elevated urinary triclosan (TCS), bisphenol A (BPA) and bisphenol S (BPS) levels were associated with increased risk of thyroid cancer (all P for trends < 0.05), and the adjusted odds ratios (ORs) comparing the extreme exposure groups were 3.52 (95% confidence interval (CI): 2.08, 5.95), 2.06 (95% CI: 1.06, 3.97) and 7.15 (95% CI: 3.12, 16.40), respectively. Positive associations were also observed between urinary TCS, BPA and BPS and three oxidative stress biomarkers measured by 8-hydroxy-2′-deoxyguanosine (8-OHdG), 8-iso-prostaglandin F2α (8-isoPGF2α) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA), as well as between urinary 8-isoPGF2α and HNE-MA and the risk of thyroid cancer. Mediation analysis showed that urinary 8-isoPGF2α mediated 28.95%, 47.06% and 31.08% of the associations between TCS, BPA and BPS exposures and the risk of thyroid cancer, respectively (all P < 0.05). Our results suggest that exposure to TCS, BPA and BPS may be associated with increased risk of thyroid cancer and lipid peroxidation may be an intermediate mechanism. Further studies are warranted to confirm the findings.